Many animals, including insects and vertebrates, rely on their olfactory systems to interact with their environments, yet little is known about how the olfactory system translates an odor input into a behavioral output. The goal of this project is to elucidate fundamental principles of odor coding by testing a small panel of chemically similar odorants, pyrazines. The experimental plan takes advantage of the simplicity of the Drosophila larval olfactory system, which has only 21 olfactory receptor neurons and expresses only 25 odor receptor genes. An in vivo expression system will be utilized to characterize the physiological responses of the larval olfactory receptors, and a simple behavioral assay will test the larval responses to odorants. The first specific aim utilizes molecular genetics and behavior to investigate the roles of two specific receptors in eliciting behavioral responses to pyrazines. Surprisingly, two pyrazines that elicit dramatically different behavioral responses elicited remarkably similar receptor response profiles. The second specific aim will test several hypotheses of odor coding that could explain this difference in behavioral response. Several pyrazines elicit extremely long lasting responses, taking on the order of minutes to return to baseline firing rate, from two larval olfactory receptors. These supersustained responses will be characterized in the third specific aim. The results of this aim have significance for our understanding of the mechanism by which an animal navigates towards an odor source. PUBLIC HEALTH RELEVANCE: Every year, millions of people die from insect-borne illnesses such as malaria and dengue fever, and these insects find humans primarily through olfactory cues. A more detailed understanding of how insects process olfactory information could lead to new research avenues for the development of more effective insect repellents and traps.